Adachi M, Tsujimoto Y
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Oncogene. 1990 Nov;5(11):1653-7.
In follicular lymphoma the majority of t(14;18) chromosome translocations occur at the 3' region of the bcl-2 gene and are juxtaposed to the J region of the immunoglobulin heavy chain gene. Direct involvement of the putative V-(D)-J recombinase in the translocation has been proposed, since the hot spot region of the breakpoints on chromosome 18 possesses the 7/9 signal-like sequence. The 5' flanking region of bcl-2 gene is another hot spot of the translocations which are preferentially associated with chronic lymphocytic leukemia. The translocation in chronic lymphocytic leukemia results in the juxtaposition of the bcl-2 gene to various regions on the immunoglobulin light chain loci. No association of a 7/9 signal sequence and the heterogeneity of the breakpoints within the bcl-2 and IgL loci suggest that the translocations occurring at the 5'-flanking region of the bcl-2 gene might be mediated by a different mechanism from that of the t(14;18) translocation. Here we demonstrate that the breakpoints at the 5' flanking region of bcl-2 gene are surrounded by multiple alternating purine-pyrimidine elements (potential Z-DNA). The antibodies specific to Z-DNA showed that the regions containing the alternating purine-pyrimidine elements were confined to the 5' hot spot region. The data suggest that Z-DNA formation may be involved in chromosome translocations at the 5' flanking region of bcl-2 gene.
在滤泡性淋巴瘤中，大多数t(14;18)染色体易位发生在bcl-2基因的3'区域，并与免疫球蛋白重链基因的J区域并列。由于18号染色体上断点的热点区域具有7/9信号样序列，因此有人提出假定的V-(D)-J重组酶直接参与了易位过程。bcl-2基因的5'侧翼区域是易位的另一个热点，这些易位优先与慢性淋巴细胞白血病相关。慢性淋巴细胞白血病中的易位导致bcl-2基因与免疫球蛋白轻链基因座上的各个区域并列。bcl-2和IgL基因座内不存在7/9信号序列以及断点的异质性，这表明发生在bcl-2基因5'侧翼区域的易位可能是由一种与t(14;18)易位不同的机制介导的。在这里，我们证明bcl-2基因5'侧翼区域的断点被多个交替的嘌呤-嘧啶元件（潜在的Z-DNA）所包围。针对Z-DNA的特异性抗体表明，含有交替嘌呤-嘧啶元件的区域局限于5'热点区域。这些数据表明，Z-DNA的形成可能参与了bcl-2基因5'侧翼区域的染色体易位。
